Gas-permeable lens

ABSTRACT

This invention comprises a gas-permeable contact lens consisting essentially of a plasticized cellulose resin selected from a partially esterified or partially etherified cellulose polymer plasticized with a compatible plasticizer in an amount sufficient to increase the gas permeability of the cellulose resin.

BACKGROUND OF THE INVENTION

Polymethylmethacrylate (PMMA) resins have long been used for themanufacture of contact lenses because of their excellent opticalproperties and machining and molding characteristics. A majordisadvantage of PMMA resins is their very low permeability to gases suchas oxygen. Since the cornea needs a continuous supply of oxygen from theair to provide for ongoing metabolic processes, the low gas permeabilityof the PMMA resins has necessitated lens designs which ameliorate thisproblem to some degree. Design changes have included reducing thediameter of the lenses in order to decrease the amount of corneal areacovered by the impermeable material and shaping the back surface of thePMMA contact lens to provide for a pumping action and concomitant tearflow under the lens, the tears containing dissolved oxygen from the air.

While such designs have made possible the wearing of contact lenses,significant problems and limitations remain, both because of theinadequacy of the oxygen supply to the cornea and because the designsmay produce discomfort and undesirable physiological symptoms to thewearer, frequently to a degree which makes wearing of the contact lenspossible for only short periods of time or not at all.

Continued oxygen deprivation of the cornea results in edema or swellingof the cornea by excess water. This impairs vision and may result incorneal damage. In addition, while oxygen must be supplied to the corneafor its metabolic processes, carbon dioxide, a waste product of theseprocesses must be removed. The same principles apply for providing aroute for removal of carbon dioxide from the cornea as for the transportof oxygen to the cornea, when a contact lens covers the cornea.

The ideal material would provide oxygen transport to the corneaequivalent to that without a lens present on the cornea. It has beenfound, however, that the cornea can remain healthy with an oxygendelivery lower than this, provided the continuous lens wear time isappropriately curtailed. It has been well established, however, that thehigher the gas permeability, the greater the safety margin for retaininga healthy cornea, the greater the patient tolerance for the lens and thelonger the continuous wear time of the lens by the patient.

Recently, materials other than PMMA and with higher gas permeabilitieshave been used for contact lenses. These include soft hydrogels, softhydrophobic polysiloxane resins, cellulose acetate butyrate (CAB) resin,and 4-methyl pentene-1 polymer. The soft materials are very flexible.CAB is less rigid than PMMA, and poly(4-methyl pentene-1) is moreflexible than PMMA and can best be characterized as semi-rigid. Allother factors being equal, the softer and more flexible the material,the greater its wearing comfort is likely to be, although beyond acertain softness there would be no advantage.

While these other recent materials provide a significant improvement ingas permeability, they still do not provide an adequate gas permeabilityexcept for the polysiloxane lenses or hydrophilic lenses with very highwater content. Lenses made of polysiloxane resins are not successful,however, as a contact lens material because of their highhydrophobicity, making it difficult or impossible for the tears of theeye to wet the lens, thereby causing great discomfort to the wearer.Hydrophilic lenses of very high water content are very weak. Animportant limitation of contact lenses made from the flexible materialsis that in forming closely to the shape of the cornea, they do notcorrect for corneal astigmatism or other corneal conditions for whichthe lenses are worn as do the lenses made from more rigid materials.Further, each of the other recent materials noted above present variousproblems in forming, machining, and polishing the contact lens, as wellas in wearing, handling and hygienic care of the lens by the patient.

SUMMARY OF THE INVENTION

Gas-permeable lenses have been found which provide for a significanttransmission of oxygen and carbon dioxide through the lens, therebyremoving total reliance for such transmission on lens design, which atbest is inadequate; which have a gas permeability of sufficientmagnitude to provide for the metabolic needs of the cornea; which haveexcellent optical properties and provide better visual acuity thanlenses made of very flexible or soft polymers; and which can be formedby conventional machining or molding technology. The contact lenses canbe worn comfortably and continuously for many hours without adverseeffect on corneal physiology and patient tolerance. Contact lensesaccording to the present invention can be of larger diameter and may beused without producing corneal anoxia, thus permitting the reduction oflid sensation.

In addition to the foregoing, the gas-permeable contact lenses aresufficiently rigid to provide for correction of corneal astigmatism andother conditions. All of the foregoing attributes are attained whileovercoming the disadvantages of conventional PMMA lenses and other rigidor semi-rigid lenses of low gas permeability.

Briefly stated, the present invention comprises a gas-permeable contactlens consisting essentially of a plasticized cellulose resin selectedfrom a partially esterified or partially etherified cellulose polymerplasticized with a compatible plasticizer in an amount sufficient toincrease the gas permeability of the cellulose resin.

DETAILED DESCRIPTION

The gas-permeable resins from which the contact lenses of the instantinvention are made, consist essentially of a major portion of a polymerformed by partial esterification or etherification of a cellulosepolymer and a minor portion of a compatible, relatively low molecularweight plasticizer which has the property of increasing the gaspermeability of the aforesaid polymer. The plasticizer is incorporatedinto the cellulose ester or ether polymer by mechanical mixing andblending techniques which are conventional in the plastics industry.

The blended composition is referred to herein as the "resin". Theresulting resin formed by blending the plasticizer and cellulose polymermust show an increased gas permeabiliy without sacrifice in otherphysical properties essential for a suitable contact lens material.Thus, the plasticizer must not be excessively extractable from the resinby its continued exposure to the saline fluids of the eye. The lighttransmission of the resin must be high so that vision is not impairedand this high light transmission must be maintained after continuedexposure to the fluids of the eye. The resin desirably should bemachineable or moldable on conventional equipment and must acceptpolishing without being scratched. Even if the contact lens is made by amolding process, there are still edge finishing operations which requirethe resin to be machineable. If the resin is too soft it may flowexcessively during machining as the result of the frictional heatproduced, causing distorted lenses with poor optics. This can bealleviated to some extent by the use of proper coolants during machiningand, in fact, the useable compositions can be extended by suchtechniques. The contact lens formed from the resin must be stable inthat it retains its dimensions, such as base curve and power, over longperiods of handling and use.

Thus, it is an essential feature of the resins of the present invention,formed by combination of cellulosic polymers and plasticizers, that highgas permeability is obtained without deterioration of other essentialoptical and physical properties.

The cellulose polymers used must be transparent and clear in order to besuitable for optical purposes. If the ester type is used, it ispreferred to use one esterified with at C₂ to C₄ .[.fatting.]..Iadd.fatty .Iaddend.acid; most suitable are the partially esterifiedcellulosic polymers wherein the ester groups are predominantlypropionate and butyrate. Generally, such cellulose ester polymerscontain a minor proportion of acetate ester groups; i.e., no more thanabout 25% .Iadd.by weight .Iaddend.of the ester groups in the polymer,in combination with the predominant ester groups. Also suitable are theether derivatives of cellulose, namely, ethyl cellulose and ethoxyethylcellulose. .[.The degree of substitution of the cellulose esterpolymers, i.e., the percentage of hydroxyl groups in the cellulosepolymer which are converted to ester groups, range from 20% to 60%, withthe preferred range being 40% to 50%. The degree of substitution for theethyl cellulose and ethoxyethyl cellulose range from 40% to 60% withthe.]. .Iadd.The extent to which hydroxyl groups in the cellulosepolymer are converted to ester groups is expressed herein as percent byweight of ester in the final esterified polymer and ranges from 20% to60% with the preferred range being 40% to 50%. The extent to whichhydroxyl groups in the cellulose polymer are converted to ether groupsis expressed herein as percent by weight of ether in the finaletherified polymer and ranges from 40% to 60% with the preferred.Iaddend.range being 45% to 50%. These unplasticized cellulose derivedpolymers are hereinafter referred to as the cellulose "base" polymers orsimply base polymer.

Generally, the higher the degree of substitution of the base polymer,the higher the oxygen permeability. However, as the degree ofsubstitution increases, the polymer becomes softer and, at some point,it may be difficult to machine and polish and carry out othermanufacturing operations thereon in a normal temperature environment.The useable degree of substitution range of the base polymer can beincreased by the use of external coolants or a low temperature workingenvironment during machining and other manufacturing operations.Mixtures of base polymers may be used for the purpose of optimizing aresin composition. Although the type of base resin is an important partof this invention, the method of synthesis or manufacture of such resindoes not form a part of this invention. Many such resins arecommercially available. Typically, such cellulose derivatives areprepared by esterification of cotton linters with a mixture of the acidand acid anhydrides concerned with an acid catalyst. For example,cellulose acetate propionate is prepared by esterifying cotton linterswith propionic anhydride, acetic acid and propionic acid with a sulfuricacid catalyst.

The other essential component of the resin of the instant invention is acompatible plasticizer. A mixture of one or more plasticizers may beused to optimize the composition. Suitable plasticizers are relativelylow molecular weight organic esters. Such esters include the productsformed from mono or poly acids with linear or branched-chain monohydroxyalcohols or polyols. These esters may be formed by the reaction ofanhydrides or acid chlorides rather than the corresponding acids.However, this invention is not intended to be limited by the method ofmanufacture of the ester, and the above reference to acids and alcoholsis a convenient way of designating the composition. Examples of suitablearomatic mono and poly acids are benzoic acid and phthalic acid with oneand two esterifiable groups, respectively. Such aromatic acids maycontain other substituent groups in the aromatic ring to modify theproperties of the resulting plasticizer. Examples of suitable aliphaticacids are fatty acids with less than 20 carbon atoms, e.g., acetic,propionic, butyric, lauric, palmitic, stearic and crotonic acids,dicarboxylic acids such as adipic, azeleic, and sebacic, andhydroxy-substituted carboxylic acids such a citric and ricinoleic.

Example of suitable monohydroxy alcohols are the straight andbranched-chain aliphatic alcohols containing from one to 20 carbonatoms. Examples of suitable alcohols are methyl alcohol, ethyl alcohol,butyl alcohol, hexyl alcohol, n-octyl alcohol, 2-ethylhexyl alcohol,decyl alcohol, octadecyl alcohol. The alcohols may contain more than onehydroxy grup, i.e., they may be polyols, examples of which are ethylene,diethylene and dipropylene glycols, butanediol and glycerol. Examples ofsuitable aromatic alcohols are benzyl alcohol and phenol. The esters maybe mono, di, tri or higher substituted esters of multifunctional acidsor multifunctional alcohols. By way of illustration, specific examplesof suitable plasticizers include diethyl phthalate, dibutyl phthalate,diisobutyl phthalate, dihexyl phthalate, dioctyl phthalate, butylbenzylphthalate, dodecyl phthalate, diethyl adipate, dibutyl adipatediisobutyl adipate, dihexyl adipate, dioctyl adipate, dibutyl azelate,dihexyl azelate, dioctyl azelate, dibutyl sebacate, dioctyl sebacate,butyl benzoate, glyceryl triacetate .[.(triacitin).]..Iadd.(triacetin).Iaddend., glyceryl tributyrate, dibutyl citrate,tributyl citrate, butyl stearate, and glycerylmonooleate.

Examples of plasticizers other than esters of organic acids arechlorinated paraffins; phosphoric acid derivatives such as tributyl,triphenyl and trioctyl phosphates; epoxidized vegetable oils, such asepoxidized soybean oil, and polymeric plasticizers such as polyalphamethyl styrene and polyesters.

The preferred embodiment of this invention is based on the organic esterplasticizers previously described.

The particular plasticizer type or mixture of plasticizers used must becompatible with the cellulose base polymer. By plasticizer compatibilityis meant that the resin containing the particular plasticizer appears asa single homogeneous species and the plasticizer does not substantiallymigrate out of the resin under use conditions. If the plasticizer isincompatible, the resin will lack high optical clarity. Someplasticizers may give an optically clear resin when in dry form, butwhen subjected to a simulated eye fluid, such as isotonic saline, forlong periods of time, the optical clarity may diminish below therequirement for a contact lens.

The plasticizer type must be such as to not migrate out of the basecellulose polymer when immersed in the fluids of the eye. If migrationoccurs, the properties of the resin, such as gas permeability willrevert to that of the base polymer, the resin may become embrittled, theoptical parameters of the lens made from the resin will change to apoint of uselessness and the migrating species might conceivablyirritate the eye.

The particular plasticizer or mixture of plasticizers used must providethe increased gas permeability at concentrations which do notdeteriorate other desirable properties, as further discussed below.

As to amount of plasticizer to be added to the base polymer to producethe resin composition, it has been found that increasing the plasticizercontent usually increases the gas permeability. With increasingplasticizer concentrations, the resulting resin increases in softnessand at some point becomes unsuitable for the manufacture of contactlenses. The range of acceptable plasticizer concentration may beincreased by modifications in manufacturing techniques. An excessiveamount of plasticizer in the resin may also decrease the stability ofthe lens made therefrom. Thus, the optical parameters such as base curveradius and power may change due to cold flow of the lens material. Thecontact lens in the eye is on a temperature environment of about 37° C.The lens material must resist any temporary or permanent opticaldistortion at this temperature, such as may be caused by an excessiveamount of plasticizer. It is evident, therefore, that the amount ofplasticizer used must be optimized to give the maximum gas permeabilitypossible, while minimizing the undesirable consequences of an excessiveplasticizer concentration.

Generally, it has been found that 3% to 25% of plasticizer based on theweight of the final resin produces the desirable results while 8% to 20%is the preferred range when using the plasticizers of the presentinvention.

The plasticizer and resin are combined with conventional plasticsprocessing equipment. Typically, the cellulose base polymer is in powderform. This powder and the plasticizer are first mixed together untilhomogeneous, in a ribbon blender or ball mill or sigma blade mixer orequivalent mixing equipment. During this operation adjuvants such asantioxidants or lubricants may be added as a processing aid for thesubsequent manufacturing steps. This homogeneous mixture is thenintensively mixed at high temperature in a plastic extruder or Banburymixer, or the like, until a homogeneous melt is formed. This melt issheeted through rolls and diced to form cubes or pellets. Alternatively,the melt from the extruded directly into strands which are cut intosmall cylinders or pellets.

The aforementioned pellets can be used for preparation of the contactlenses of this invention. The pellets may be formed into cylindrical rodform or sheet form on a plastic extruder. From these rods or sheets,small cylinders are cut to give so-called lens bonnets from which thecontact lens can be machined. Alternatively, the pellets may be directlymolded into bonnet form on a plastics blow molding machine, or thecontact lens may be directly molded. In the latter instance, a largenumber of molds is required to cover the required range of base curveradii and powers. The method of forming the plastic, preparing bonnetsand machining or molding lenses are conventional. Machining coolants orexternally controlled temperature in the working environment may be usedto extend the range of resin softness that can be used.

The essential feature of the resins of this invention and the contactlenses made therefrom is that the gas permeability be increased overthat of the cellulose base polymer. Oxygen permeability is measured byintervening the lens as part of the electrolyte in a platinum-silverchloride electrolytic oxidation-reduction cell. The current flow throughthis cell is proportional to the amount of oxygen passing through thelens which is reduced at the platinum electrode. The apparatus andmethod have been described by Fatt in the book Polarographic OxygenSensor, CRC Press, Inc., 1976. In the examples that follow, the instantinention will be demonstrated by measurement of oxygen permeability oncontact lenses or films made from various resin compositions.

The following examples are given to illustrate the best modes forcarrying out the present invention in which the plasticizers used are ofcommercial grade, but are not to be construed as restricting the scopethereof.

EXAMPLES 1-3

A cellulose acetate ester base polymer comprising about 3% acetate estergroups, and about 45% propionate ester groups was used. The base polymeris blended with different amounts of dihexyl azelate. This resin wasused in the form of molding pellets which were then molded on aconventional injection molding machine into eight cylinder bonnets of0.75 inch in diameter and 0.2 inch thickness. Contact lenses of about0.2 mm center thickness were made from the bonnets and oxygenpermeability constants were measured. The results are shown below:

    ______________________________________                                                  Weight % Dihexyl Azelate.sup.1                                                                   Permeability                                     Example No.                                                                             Plasticizer         Constant.sup.2                                  ______________________________________                                        1         0                  3.4 × 10.sup.-11**                         2          3*                4.3 × 10.sup.-11                           3         12*                6.9 × 10.sup.-11                           ______________________________________                                         Footnotes:                                                                    .sup.1 Weight percent of dihexyl azelate plasticizer based on the total       weight of base resin plus plasticizer.                                        ##STR1##                                                                      *The 12% plasticized resin is available under the trade name Tennite          Propionate 350A, flow grade H2 and the 3% plasticized resin as Tennite        Propionate 350A, flow grade H6.                                                **The permeability constant for 0% dihexyl azelate was obtained by           extrapolation.                                                           

Examples 1 to 3 show the effect of increasing the amount of plasticizeron the permeability. On this same scale, a polymethyl methacrylate lenswould give a permeability constant of 0.1×10⁻¹¹ or less. The resin ofExample 3 gives a good compromise between high permeability,machineability and stability. Contact lenses made from the resin ofExample 3 were tested clinically on a patient with good results.

EXAMPLES 4-7

The procedure of Examples 1 to 3 was repeated except that the base resinused was a cellulose ester comprising about 38% butyrate ester groupsand about 13% acetate ester groups, and the plasticizer was dioctyladipate. The results are shown below:

    ______________________________________                                                    Weight % Dioctyl                                                                              Permeability                                      Example No. Adipate.sup.1    Constant.sup.2                                   ______________________________________                                        4            0*              4.0 × 10.sup.-11                           5            5*              5.8 × 10.sup.-11                           6           17*              9.5 × 10.sup.-11                           7           21*             13.9 × 10.sup.-11                           ______________________________________                                         Footnotes:-                                                                   .sup.1 Weight % dioctyl adipate (di(2ethylhexyl)adipate) plasticizer base     on the total weight of base resin plus plasticizer.                           ##STR2##                                                                      *The resins shown starting in order from 0% are available under the trade     names Tennite 264A, flow grade H4, 264A, flow grade H2, 264A, flow grade      MS and 264A, flow grade S2.                                              

The preferred cellulose ester base resins contain 30% to 50% of themajor substituent ester group, i.e., propionate or butyrate groups and0% to 15% of the minor substituent ester group, i.e., the acetate group.The preferred plasticizer content of the final resin varies with thetype of plasticizer and the type of base resin, but preferably gives apermeability constant of at least 5×10⁻¹¹ (cm² /sec) (ml O₂ /ml mm Hg).

EXAMPLES 8-10

The procedure of Examples 1 to 3 was repeated except that the base resinis a cellulose ether (ethyl cellulose) comprising 48% ethyl ether groupsand the plasticizer used was triglyceryl acetate (triacetin). Also, thebase resin was used in powder form and films of about 0.2 mm. thicknesswere cast from a solution of the powdered resin in benzene. Permeabilitymeasurements were made on these dried films. The results are shownbelow:

    ______________________________________                                                    Weight % Triacetin                                                                            Permeability                                      Example No. Plasticizer.sup.1                                                                              Constant.sup.2                                   ______________________________________                                         8*          0              5.7 × 10.sup.-11                            9           10              6.9 × 10.sup.-11                            10          30              6.0 × 10.sup.-11                            ______________________________________                                         Footnotes:                                                                    .sup.1 Weight % same basis as Examples 1-7.                                   .sup.2 Same units as in previous examples.                                    *The resin with 0% plasticizer is available from Hercules Inc. as Number      n50.                                                                     

EXAMPLES 11-14

The procedure of Examples 8 to 10 was repeated except that the ethylcellulose base resin used was of 49% ethoxy content and the plasticizerused was dibutyl phthalate. The results are shown below:

    ______________________________________                                                  Weight % Dibutyl   Permeability                                     Example No.                                                                             Phthalate Plasticizer.sup.1                                                                       Constant.sup.2                                  ______________________________________                                        11         0*                6.9                                              12        5                  6.9                                              13        10                 7.8                                              14        20                 7.3                                              ______________________________________                                         Footnotes:                                                                    .sup.1 Weight basis is the same as in Examples 8 to 10.                       .sup.2 Units are the same as in previous examples.                            *The base resin with 0% plasticizer is available from Dow Chemical Co.        under the number ethyl cellulose, Dow SP 100.                            

In Examples 8 through 14 there appears to be a maximum in thepermeability constant at about 10% plasticizer concentration.

While the invention has been described in connection with the preferredembodiments, it is not intended to limit the invention to the particularforms set forth, but, on the contrary, it is intended to cover suchalternatives, modifications, and equivalents as may be included withinthe spirit and scope of the invention as defined by the appended claims.

What is claimed is:
 1. A transparent optically clear gas-permeablecontact lens consisting essentially of a plasticized cellulose resinselected from a partially esterified or partially etherified cellulosepolymer plasticized with a compatible plasticizer in an amountsufficient to increase the oxygen permeability of the cellulose resin atleast about 13% higher than that of the unplasticized cellulose resinbut below that at which the optical and physical properties of the lensare substantially adversely affected.
 2. The contact lens of claim 1wherein the cellulose .[.polymer.]. .Iadd.resin prior to plasticization.Iaddend.is a partially esterified cellulose polymer in which from about20% to 60% .[.of the hydroxyl groups in the polymer are esterifiedwith.]. .Iadd.by weight thereof is esters of .Iaddend.a C₂ to C₄ fattyacid.
 3. The contact lens of claim 1 wherein the partially esterifiedcellulose .[.polymer.]. .Iadd.resin prior to plasticization .Iaddend.isselected from cellulose acetate butyrate, cellulose acetate propionate,or mixtures thereof, in which 40% to 50% .[.of the hydroxyl groups inthe polymer are esterified.]. .Iadd.by weight thereof is esters,.Iaddend.and in which the predominant ester group in each .[.polymer.]..Iadd.resin prior to plasticization .Iaddend.is, respectively, butyrateand propionate.
 4. The contact lens of claim 1 wherein the plasticizeris selected from low molecular weight organic esters, chlorinatedparaffins, phosphoric acid derivatives, epoxidized vegetable oil,polymeric plasticizers, and mixtures thereof.
 5. The contact lens ofclaim 1 wherein the .[.polymer.]. .Iadd.resin prior to plasticization.Iaddend.is selected from cellulose acetate butyrate, cellulose acetatepropionate, or mixtures thereof, in which about 40% to 50% .[.of thehydroxyl groups in the polymer are esterified.]. .Iadd.by weight thereofis esters .Iaddend.and in which the acetate ester group comprises nomore than about 25% .Iadd.by weight .Iaddend.of the ester groups in thepolymer, and in which the plasticizer is a low molecular weight organicester formed from mono or poly acids with linear or branched-chainmonohydroxy alcohols or polyols; the plasticizer being used in an amountof from about 3% to 25% by weight based on the total weight ofplasticizer and polymer.
 6. The contact lens of claim 1 wherein thecellulose resin .Iadd.prior to plasticization .Iaddend.is a partiallyetherified cellulose polymer selected from ethyl cellulose, ethoxyethylcellulose, or mixtures thereof, in which from about 40% to 60% .[.of thehydroxyl groups in the polymer are etherified.]. .Iadd.by weight thereofis ethers. .Iaddend.
 7. The contact lens of claim 6 wherein theplasticizer is selected from low molecular weight organic esters,chlorinated paraffins, phosphoric acid derivatives, epoxidized vegetableoils polymeric plasticizers, and mixtures thereof.
 8. The contact lensof claim 6 wherein .Iadd.the cellulose resin prior to plasticization isa partially etherified cellulose polymer in which .Iaddend.45% to 50%.[.of the hydroxyl groups are etherified.]. .Iadd.by weight thereof isethers .Iaddend.and the plasticizer is a low molecular weight organicester formed from mono or poly acids with linear or branched-chainmonohydroxy alcohols or polyols; the plasticizer being used in an amountof from about 3% to 25% by weight, based on the total weight ofplasticizer and polymer.
 9. The contact lens of claim 1 wherein thecellulose polymer is cellulose acetate propionate and the plasticizer isdihexyl azelate, said plasticizer being present in an amount from about3% to 25% by weight based on the total weight of plasticizer andpolymer.
 10. The contact lens of claim 1 wherein the cellulose polymeris cellulose acetate butyrate and the plasticizer isdi(2-ethylhexyl)adipate, said plasticizer being present in an amountfrom about 3% to 25% by weight based on the total weight of plasticizerand polymer.